U.S. patent application number 11/994818 was filed with the patent office on 2008-12-25 for apparatus and method for measuring constituent concentrations within a biological tissue structure.
This patent application is currently assigned to FERLIN MEDICAL LTD.. Invention is credited to Christopher Paul Hancock.
Application Number | 20080319285 11/994818 |
Document ID | / |
Family ID | 36928167 |
Filed Date | 2008-12-25 |
United States Patent
Application |
20080319285 |
Kind Code |
A1 |
Hancock; Christopher Paul |
December 25, 2008 |
Apparatus and Method for Measuring Constituent Concentrations
within a Biological Tissue Structure
Abstract
Apparatus for minimally invasively measuring concentrations of
constituents contained within a biological tissue structure
includes a microwave energy source arranged generate a range of
microwave frequencies, a first antenna coupled to the microwave
energy source and arranged to transmit at least a portion of the
microwave energy into the tissue structure, a second antenna
arranged to receive at least a portion of the microwave energy
transmitted through the tissue structure, a signal processor
arranged to determine the resonant frequency of the received
microwave energy, and a data processor arranged to provide an
output of the concentration of constituents within the biological
tissue structure according to the determined resonant
frequency.
Inventors: |
Hancock; Christopher Paul;
(Bath & North East Somerset, GB) |
Correspondence
Address: |
MARSHALL, GERSTEIN & BORUN LLP
233 S. WACKER DRIVE, SUITE 6300, SEARS TOWER
CHICAGO
IL
60606
US
|
Assignee: |
FERLIN MEDICAL LTD.
Gwynedd
GB
|
Family ID: |
36928167 |
Appl. No.: |
11/994818 |
Filed: |
July 6, 2006 |
PCT Filed: |
July 6, 2006 |
PCT NO: |
PCT/GB2006/002514 |
371 Date: |
July 9, 2008 |
Current U.S.
Class: |
600/309 ;
600/430 |
Current CPC
Class: |
A61B 5/0507 20130101;
A61B 5/14546 20130101; A61B 5/14532 20130101; A61B 5/05
20130101 |
Class at
Publication: |
600/309 ;
600/430 |
International
Class: |
A61B 5/145 20060101
A61B005/145 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 6, 2005 |
GB |
0513810.2 |
Jul 26, 2005 |
GB |
0515277.2 |
Claims
1. Apparatus for minimally invasively measuring concentrations of
constituents contained within a biological tissue structure, the
apparatus comprising: a microwave energy source arranged to
generate a range of microwave frequencies; a first antenna coupled
to the microwave energy source and arranged to transmit at least a
portion of the microwave energy into the tissue structure; a second
antenna arranged to receive at least a portion of the microwave
energy transmitted through the tissue structure; a signal processor
arranged to determine the resonant frequency of the received
microwave energy; and a data processor arranged to provide an
output of the concentration of constituents within the biological
tissue structure according to the determined resonant
frequency.
2. Apparatus according to claim 1, wherein the signal processor is
arranged to measure the magnitude response of the ratio of the
received microwave energy to the transmitted microwave energy and
determine the frequency at which a minima or maxima in the
magnitude response occurs, said frequency being the resonant
frequency.
3. Apparatus according to claim 2, wherein the signal processor is
arranged to determine the 3 dB bandwidth of the magnitude response
for the frequency of the minima or maxima and thereby derive the Q
factor of the biological tissue structure.
4. Apparatus according to claim 3, wherein the data processor is
arranged to correlate the derived value of Q factor to a
constituent concentration value.
5. Apparatus according to claim 1, wherein the signal processor is
arranged to measure the phase response of the ratio of the received
microwave energy to the transmitted microwave energy and determine
the frequency at which a minima or maxima in the phase response
occurs, said frequency being the resonant frequency.
6. Apparatus according to claim 1, wherein the first and second
antennas comprise a single transceiver wherein the received
microwave energy comprises reflected microwave energy.
7. Apparatus according to claim 6, wherein the apparatus further
comprises a reflector plate arranged to reflect microwave energy
transmitted from the single antenna back to said antenna.
8. Apparatus according to claim 1, wherein the microwave energy
source is arranged to generate microwave energy over a range of
frequencies such that at the resonant frequency the biological
tissue structure forms a single wave resonance cavity.
9. Apparatus according to claim 1, wherein the microwave energy
source is arranged to generate microwave energy over a range of
frequencies such that at the resonant frequency the biological
tissue structure forms a half wave resonance cavity.
10. Apparatus according to claim 1, wherein the microwave energy
source is arranged to generate microwave energy within the
frequency range of 8 GHz to 18 GHz.
11. Apparatus according to claim 10, wherein the microwave source
is arranged to generate microwave energy within a number of
frequency bandwidths within said frequency range.
12. Apparatus according to claim 1, wherein the first and second
antennas comprise patch antennas, each antenna having a radiating
patch and a microwave feed line.
13. Apparatus according to claim 12, wherein the microwave feed
line comprises a micro-strip connected to the radiating patch.
14. Apparatus according to claim 12, wherein the microwave feed
line comprises a coaxial feed.
15. Apparatus according to claim 12, wherein the microwave feed
line is electromagnetically coupled to the radiating patch.
16. Apparatus according to claim 12, wherein the radiating patch
includes an annular slot formed therein.
17. Apparatus according to claim 1, wherein the first and second
antennas comprise spiral antennas.
18. Apparatus according to claim 1, wherein the first and second
antennas comprise waveguide antennas.
19. Apparatus according to claim 1, wherein the first and second
antennas are arranged to be non-invasively attached to the
biological tissue structure.
20. Apparatus according to claim 1, wherein the first and second
antennas comprise one of waveguide antennas or coaxial monopole
antennas, each antenna having an inner and an outer conductor.
21. Apparatus according to claim 20, wherein the inner antenna
comprises a needle like structure arranged to pierce the surface
layer of the biological tissue.
22. Apparatus according to claim 21, wherein the inner antenna is
hollow and is arranged to be in fluid communication with a fluid
source.
23. Apparatus according to claim 21, wherein the outer antenna is
arranged to pierce the surface layer of the biological tissue.
24. Apparatus according to claim 1, wherein the data processor is
arranged to correlate the determined resonant frequency to the
thickness of the biological tissue structure to provide the
constituent concentration information.
25. Apparatus according to claim 24, wherein a value for the
biological tissue structure thickness is provided as a
predetermined input parameter.
26. Apparatus according to claim 24, wherein the signal processor
is arranged to measure the capacitance of the biological tissue
structure between the first and second antennas, from which the
thickness value is derived.
27. Apparatus according to claim 1, wherein said first and second
antennas are arranged to be attached to either side of at least one
of an earlobe or the skin interconnecting a thumb and
forefinger.
28. Apparatus according to claim 1, wherein at least the microwave
source, and first and second antennas are arranged as a portable
assembly for wearing by an individual.
29. Apparatus according to claim 1, wherein at least one of the
signal processor and data processor comprise one from the list of a
personal computer, a laptop computer, a mobile computer and a
mobile telephone.
30. Apparatus according to claim 1, wherein the constituent
concentration comprises at least blood-glucose, blood-alcohol or
cholesterol.
31. A method of minimally invasively measuring concentrations of
constituents contained within a biological tissue structure, the
method comprising: generating a range of microwave frequencies;
transmitting at least a portion of the generated microwave energy
into the tissue structure; receiving at least a portion of the
microwave energy transmitted through the tissue structure;
determining the resonant frequency of the received microwave
energy; and providing an output of the concentration of
constituents within the biological tissue structure according to
the determined resonant frequency.
32. The method of claim 31, wherein the magnitude response of the
ratio of the received microwave energy to the transmitted microwave
energy is measured and the frequency at which a minima or maxima in
the magnitude response occurs determined, said frequency being the
resonant frequency.
33. The method of claim 32, wherein the 3 dB bandwidth of the
magnitude response for the frequency of the minima or maxima is
determined and therefore the Q factor of the biological tissue
structure is derived.
34. The method of claim 33, wherein the derived value of Q factor
is correlated to a constituent concentration value.
35. The method of claim 31, wherein the phase response of the ratio
of the received microwave energy to the transmitted microwave
energy is measured and the frequency at which a minima or maxima in
the phase response occurs is determined, said frequency being the
resonant frequency.
36. The method of claim 31, wherein the microwave energy generated
over a range of frequencies such that at the resonant frequency the
biological tissue structure forms a single wave resonance
cavity.
37. The method of claim 31, wherein the microwave energy generated
over a range of frequencies such that at the resonant frequency the
biological tissue structure forms a half wave resonance cavity.
38. The method of claim 31, wherein the microwave energy is
generated within the frequency range of 8 GHz to 18 GHz.
39. The method of claim 31, wherein the microwave energy is
generated within a number of frequency bandwidths within said
frequency range.
40. The method of claim 31, wherein the determined resonant
frequency is correlated to the thickness of the biological tissue
structure to provide the constituent concentration information.
41. The method of claim 40, wherein a value for the biological
tissue structure thickness is provided as a predetermined input
parameter.
42. The method of claim 40, wherein the capacitance of the
biological tissue structure is measured, from which the thickness
value is derived.
43. The method of claim 31, the biological tissue structure
comprises one of an earlobe or the skin interconnecting a thumb and
forefinger.
44. The method of claim 31, wherein the constituent concentration
comprises at least blood-glucose, blood-alcohol or cholesterol.
Description
BACKGROUND
[0001] Diabetes mellitus (diabetes) is a disease in which the body
does not produce or properly use insulin. In simplest terms,
insulin is a hormone needed to convert sugar and starches into
energy. In effect, insulin is the hormone that unblocks cells of
the body, allowing glucose to enter these cells to provide food to
keep them alive. If glucose cannot enter the cells, the glucose
concentration in the body builds up and, without treatment, the
cells within the body end up starving to death. The measurement of
blood-glucose is thus perhaps the most important measurement in
medicine, as diabetes has immense public health implications.
Diabetes is currently a leading cause of disability and death
throughout the world.
[0002] Diabetes sufferers cannot moderate the amount of glucose in
their bloodstream automatically in the manner non-sufferers can.
Therefore to prevent the onset and the progression of complications
associated with diabetes, sufferers of both Type I (where the body
fails to produce sufficient insulin) and Type II diabetes (where
the body develops a resistance to the action of its own insulin)
are advised to closely monitor the concentration of glucose in
their bloodstream. If the concentration is outside the normal
healthy range, the patient needs to adjust his or her insulin
dosage or sugar intake to counter the risk of diabetic
complications.
[0003] The most common method of measuring blood-glucose level
requires blood to be withdrawn from the patient. The conventional
procedure involves pricking the finger, or other body part, to
withdraw blood, and then to test the blood for glucose levels,
either by depositing one or more drops onto a reagent carrier strip
having a glucose testing substance thereon that changes colour or
shading in correspondence with the detected amount of
blood-glucose, or by the use of a portable, often hand held,
electronic testing device. However, many people find this method
either inconvenient, painful, difficult to perform or simply
unpleasant.
[0004] A further common glucose monitoring method involves urine
analysis. This method tends to be most inconvenient and may not
reflect the current status of the blood-glucose level due to the
fact that glucose appears in the urine only after a significant
period of elevated levels of blood-glucose.
[0005] Another technique involves using implantable medical devices
to measure cardiac signals. In one such invention, the
blood-glucose levels are determined based on T-wave amplitude and
the QT-interval. The disadvantage of this method is that the
instrument has to be inserted inside the human body and so a
complex medical procedure may need to be performed. Also, the
patient would need to be admitted to hospital and may need to stay
for a few days. Additionally, this device would be classified as a
class III medical device because it is inserted inside the body. A
class III medical device is categorised as a high-risk device and
would need to go through stringent testing and validation
procedures before being granted approval by the medical devices
regulatory bodies to enable it to be put into regular use.
[0006] A further measurement technique involves the sampling of
interstitial fluid from the skin. A system developed by Cygnus
Inc., known as the GlucoWatch G2 Biographer, uses low levels of
electrical current to extract glucose molecules through the skin.
The glucose is extracted from interstitial fluid that surrounds
skin cells, rather than from blood. The system gathers and analyses
current-time and charge time data to calculate blood-glucose level
information. The drawbacks of this system are; it is still
necessary to perform the finger prick test in order to calibrate
the system and it is still necessary to withdraw a small amount of
biological fluid (interstitial fluid) from the body during normal
operation.
[0007] Many attempts have also been made to develop a painless,
patient friendly, cost effective, non-invasive instrument to
monitor blood-glucose levels. The non-invasive approaches
considered include: electrochemical, spectroscopic technologies,
such as near infrared spectroscopy, Ramen Spectroscopy and small
scale NMR, measurements on lacrimal fluid (self-sampled tears), and
acoustic velocity measurement techniques. However, none of these
methods appear to have produced a marketable device or method for
in-vivo measurement of blood-glucose level that is sufficiently
accurate, reliable, patient friendly, convenient and cost-effective
enough to be used in routine use.
SUMMARY OF THE INVENTION
[0008] According to a first aspect of the present invention there
is provided apparatus for minimally invasively or non-invasively
measuring concentrations of constituents contained within a
biological tissue structure, the apparatus comprising a microwave
energy source arranged to generate a range of microwave
frequencies, a first antenna coupled to the microwave energy source
and arranged to transmit at least a portion of the microwave energy
into the tissue structure, a second antenna arranged to receive at
least a portion of the microwave energy transmitted through the
tissue structure, a signal processor arranged to determine the
resonant frequency of the received microwave energy and a data
processor arranged to provide an output of the concentration of
constituents within the biological tissue structure according to
the determined resonant frequency and the associated
characteristics of the measured response.
[0009] The signal processor may be arranged to measure the
magnitude response of the ratio of the received microwave energy to
the transmitted microwave energy and determine the frequency at
which a minima or maxima in the magnitude response occurs, said
frequency being the resonant frequency. The signal processor may
additionally be arranged to determine the 3 dB bandwidth of the
magnitude response for the frequency of the minima or maxima and
thereby derive the Q factor of the biological tissue structure. The
data processor may additionally be arranged to correlate the
derived value of Q factor to a constituent concentration value. The
data processor may be additionally arranged to determine other
characteristics such as slope or gradient of the measured data.
[0010] The signal processor may be further arranged to measure the
phase response of the ratio of the received microwave energy to the
transmitted microwave energy and determine the frequency at which a
minima or maxima in the phase response occurs, said frequency being
the resonant frequency.
[0011] The first and second antennas may comprise a single
transceiver wherein the received microwave energy comprises
reflected microwave energy. Preferably, a reflector plate is
arranged to reflect microwave energy transmitted from the single
antenna back to said transceiver. In this arrangement, a resonant
cavity is set-up between the antenna and the plate.
[0012] The microwave energy source may be arranged to generate
microwave energy over a range of frequencies such that at the
resonant frequency the biological tissue structure forms a single
wave resonant cavity.
[0013] Preferably, the microwave energy source is arranged to
generate microwave energy over a range of frequencies such that at
the resonant frequency the biological tissue structure forms a half
wave resonant cavity.
[0014] More preferably, the microwave source is arranged to
generate microwave energy within the frequency range of 1 GHz to
100 GHz. Even more preferably, over the frequency range of between
8 GHz and 18 GHz.
[0015] The microwave source may be arranged to generate microwave
energy within a number of frequency bandwidths within said
frequency range.
[0016] The first and second antennas may each comprise a patch
antenna, each antenna having a radiating patch and a microwave feed
line. The microwave feed line may comprise a micro-strip line
connected to the radiating patch, a coaxial feed or the microwave
feed line may be electromagnetically coupled to the radiating
patch. Additionally, the radiating patch may include an annular
slot formed therein.
[0017] Alternatively, wherein the first and second antennas
comprise spiral or waveguide antennas.
[0018] Preferably, the first and second antennas are arranged to be
non-invasively attached to the biological tissue structure.
Alternatively, the first and second antennas may comprise one of
waveguide antennas or coaxial monopole antennas, each antenna
having an inner and an outer conductor, where the inner conductor
preferably comprises a needle like structure arranged to pierce the
surface layer of the biological tissue. Additionally, the outer
conductor may be arranged to pierce the surface layer of the
biological tissue.
[0019] The data processor may be arranged to correlate the
determined resonant frequency to the thickness of the biological
tissue structure to provide the constituent concentration
information. A value for the biological tissue structure thickness
may be provided as a predetermined input parameter or alternatively
the signal processor may be arranged to measure the capacitance of
the biological tissue structure between the first and second
antennas, from which the thickness value may be derived. Other
methods of measuring the thickness include a resistive method where
resistance is proportional to thickness and an optical displacement
sensor.
[0020] The first and second antennas are preferably arranged to be
attached to either side of at least one of an earlobe or the skin
interconnecting a thumb and forefinger. Other regions of the
anatomy that are rich in blood flow and simple in structure may
also be considered.
[0021] Preferably, at least the microwave source, and first and
second antennas are arranged as a portable assembly for wearing by
an individual.
[0022] At least one of the signal processor and data processor may
comprise one from the list of a personal computer, a laptop
computer, a mobile computer, a wrist watch with a microprocessor
and a mobile telephone.
[0023] The constituent concentration preferably comprises at least
blood-glucose, blood-alcohol or cholesterol.
[0024] According to a second aspect of the present invention there
is provided a method of minimally invasively measuring
concentrations of constituents contained within a biological tissue
structure, the method comprising generating a range of microwave
frequencies, transmitting at least a portion of the generated
microwave energy into the tissue structure, receiving at least a
portion of the microwave energy transmitted through the tissue
structure, determining the resonant frequency of the received
microwave energy and providing an output of the concentration of
constituents within the biological tissue structure according to
the determined resonant frequency and the measured response.
[0025] The magnitude response of the ratio of the received
microwave energy to the transmitted microwave energy may be
measured and the frequency at which a minima or maxima in the
magnitude response occurs determined, said frequency being the
resonant frequency.
[0026] The 3 dB bandwidth of the magnitude response for the
frequency of the minima or maxima may be determined and therefore
the Q factor of the biological tissue structure is derived. The
derived value of Q factor may be correlated to a constituent
concentration value.
[0027] The phase response of the ratio of the received microwave
energy to the transmitted microwave energy may be measured and the
frequency at which a minima or maxima in the phase response occurs
is determined, said frequency being the resonant frequency.
[0028] The microwave energy is preferably generated over a range of
frequencies such that at the resonant frequency the biological
tissue structure forms either a single or half wave resonant
cavity. The microwave energy is preferably generated within the
frequency range of 8 GHz to 18 GHz. Additionally, the microwave
energy is generated within a number of frequency bandwidths within
said frequency range.
[0029] The determined resonant frequency may be correlated to the
thickness of the biological tissue structure to provide the
constituent concentration information. A value for the biological
tissue structure thickness may either be provided as a
predetermined input parameter or the capacitance of the biological
tissue structure may be measured, from which the thickness value
maybe derived.
[0030] Preferably, the biological tissue structure comprises one of
an earlobe or the skin interconnecting a thumb and forefinger and
the constituent concentration comprises at least blood-glucose,
blood-alcohol or cholesterol.
BRIEF DESCRIPTION OF DRAWINGS
[0031] Embodiments of the present invention will now be described,
by way of non-limiting examples only, with reference to the
accompanying figures, of which:
[0032] FIG. 1 shows a block diagram of an embodiment of the present
invention;
[0033] FIG. 2 schematically illustrates a typical biological
structure used with embodiments of the present invention;
[0034] FIG. 3 shows an embodiment of the present invention to
measure transmission and reflection characteristics in two
directions;
[0035] FIG. 4 shows an arrangement for measuring magnitude
response;
[0036] FIG. 5 shows a detailed arrangement of an embodiment of the
present invention;
[0037] FIG. 6 shows an alternative arrangement to that shown in
FIG. 5;
[0038] FIG. 7 shows an antenna arrangement according to embodiments
of the present invention with two co-axially fed patch
antennas;
[0039] FIG. 8 shows the top view of a rectangular patch antenna fed
using a micro-strip line laid on the same plane as the radiating
patch;
[0040] FIG. 9 shows a possible configuration for a pin antennas
arranged to penetrate the biological tissue;
[0041] FIG. 10 shows an arrangement for a loaded cylindrical
antenna arranged to penetrate the biological tissue;
[0042] FIG. 11 is a graph showing magnitude change results obtained
from apparatus according to embodiments of the present
invention;
[0043] FIG. 12 is a second graph showing phase change results
obtained from apparatus according to embodiments of the present
invention;
DETAILED DESCRIPTION OF THE INVENTION
[0044] FIG. 1 schematically illustrates apparatus according to a
first embodiment of the present invention. A microwave source 10 is
connected to a power control device 170, such as a PIN diode
attenuator, followed by a low power amplifier 20. The microwave
source 10 may be any suitable oscillating device, such as a voltage
controlled oscillator (VCO), dielectric resonator oscillator (DRO),
surface acoustic wave device (SAW), or frequency synthesiser. The
latter will be used in the instance where it is required to sweep
the frequency over a large range. A VCO device may be used where
the range of frequencies is more limited. Embodiments of the
present invention may be used over the microwave frequency range of
between 1 GHz and 100 GHz, subject to microwave devices available
and physical or geometrical constraints apply. In embodiments of
the present invention preferred frequency ranges are 4.45 GHz to 5
GHz (550 MHz sweep range), 5.6 GHz to 6.8 GHz (1.2 GHz sweep range)
and 13.2 GHz to 13.5 GHz (300 MHz sweep range). In some embodiments
it may be preferred to have a single microwave frequency, or a
number of discrete frequencies, in which case it is preferable to
phase lock the microwave source.
[0045] The output power of the low power amplifier 20 is preferably
less that 100 mW when operated in continuous wave (CW) mode, but
this may be increased when operated in pulse mode, where the duty
cycle can be much lower than 50%, hence the peak power can be
greater than 100 mW whilst maintaining an average power of equal to
or less than 100 mW. However, other power levels may also be used.
The output of the amplifier 20 is connected to the input of a first
directional coupler 101, whose coupled port is connected to the
input of a frequency divider (pre-scalar) 104. The orientation of
first directional coupler 101 is such that forward power from
amplifier 20 will enter the coupled port. The output from 101 is
connected to the input of a second directional coupler 60, whose
coupled port is connected to a detector/receiver unit 100. The
orientation of the second directional coupler 60 is such that
forward power from amplifier 20 will enter the coupled port. The
output from the second directional coupler 60 is connected to the
input of a third directional coupler 61, whose coupled port is also
connected to the detector/receiver unit 100. The orientation of the
third directional coupler 61 is such that reflected power will
enter the coupled port. The output from 61 is connected to the
input of a co-axial cable assembly 40, and the distal end of cable
assembly 40 is connected to a first antenna 70, which is used to
transmit microwave energy from microwave source 10, and low power
amplifier 20, into a portion of a biological tissue structure 80.
In practice, cable assembly 40 may not be required, as in certain
embodiments coupler 61 is connected directly to first antenna 70. A
second antenna 71 is connected to a matching filter 51, whose
function is to provide an impedance match between the output of the
second antenna 71 and the surface of the biological tissue
structure 80 to enable maximum power transfer into the tissue,
which will lead to the highest possible signal strength and ensure
that the signal fed into the detector 100 is above the noise floor
of said detector 100. The output from the matching filter 51 is
connected to the input of a co-axial cable assembly 41, and the
distal end of the co-axial cable 41 is connected to a third input
of the detector/receiver unit 100. In practice, the cable assembly
41 may not be required, as in certain embodiments the
detector/receiver unit 100 will be connected directly to the second
antenna 71. The matching filter 51 may be excluded from the line up
in the instance where it is not required to match the energy to the
tissue or where said the second antenna 71 has been statically
matched to the surface of said biological tissue structure 80
during manufacture. On the other hand, a second matching filter may
also be required to transfer energy more efficiently from the
microwave source 10 and low power amplifier 20 into the biological
tissue structure 80. The first and second antennas 70,71 are
preferably fixed to the biological tissue structure 80 and are
aligned using a clip arrangement 90 and fasteners 91,92. The
biological tissue structure is preferably the earlobe or the web of
the hand between the thumb and first finger, but this invention is
not limited to using these regions of the human biological
system.
[0046] The output from the frequency divider (pre-scalar) 104
provides a first input into the signal processor/controller 110,
where the output frequency produced by the microwave source 10 is
identified and stored in an internal memory. The coupled signals
from the second and third couplers 60,61 provide information
regarding the forward transmitted and forward reflected signals,
and the signal from the distal end of the second co-axial
cable-assembly 41 provides information regarding the forward
received energy after the microwave energy has passed through the
biological tissue structure 80. The difference in phase and/or
magnitude between the energy impinging on the second antenna 71 and
that transmitted from the first antenna 70 provides information
regarding the concentration of constituents contained within the
biological fluid (normally blood). The signals from the couplers 60
and 61, and the forward received signal are also fed into the
detector/receiver unit 100, where phase and magnitude information
is extracted and also fed into the signal processor/controller 110.
The phase and magnitude information is correlated with the
frequency information supplied by the frequency divider
(pre-scalar) 104 using the signal processor/controller 110 and
changes in phase and/or magnitude are calculated.
[0047] The signal processor/controller 110 is also arranged to send
a control signal to PIN attenuator 170 to control the microwave
power level and to send a control signal to the microwave source 10
to enable the output frequency to be swept. The signal
processor/controller 110 also performs noise filtering, signal
conditioning and performs any other desired signal processing and
monitoring functions in a manner known to the person skilled in the
art.
[0048] The processed information is fed into a suitable output
device 120, which presents patient information, provides the
necessary user control facilities and acts as an interface to the
outside world.
[0049] In embodiments of the present invention it is desired to
create a resonant microwave cavity within the tissue structures
between the two antennas. In preferred embodiments the distance
between the antennas is approximately 3.5-3.7 mm, as dictated by
the thickness of the tissue, which means that this needs to be a
length of a single wavelength, for example, of microwave energy for
resonance to occur (it will be appreciated that resonance may occur
at other integers or fractions of wavelengths, such as a half
wavelength). This measurement approximately matches the thickness
of skin found between the thumb and forefinger or the thickness of
the earlobe. Given the wavelength, the required frequency for
resonance is dictated by the permeability of the medium through
which the microwave energy travels. Consequently, if the frequency
of transmitted microwaves is swept over a frequency range
encompassing the resonant frequency for the given permeability of
the transmission medium, then the received energy will display
either a minimum or a maximum in its magnitude at the resonant
frequency (depending on the method of detection, the material
within the cavity and the cavity itself). However, if the
permeability of the transmission medium alters, the resonant
frequency will change. It is this characteristic that embodiments
of the present invention utilise, since the permittivity of the
tissue varies with the concentration of blood-glucose. The phase of
the microwave energy either received by a second antenna or
reflected back to the first antenna relative to the transmitted
microwave energy is also dependant on the permittivity of the
transmission medium and hence on the blood-glucose concentration in
the tissue structures. This characteristic is also utilised in
embodiments of the present invention.
[0050] The directional couplers 101,60,61 are preferably fabricated
onto a microwave dielectric substrate with copper, or another
suitable metallic coating, on both sides. The preferred arrangement
for the couplers is edge-coupled microstrip lines, although other
microwave directional couplers will be apparent to the skilled
person. The main constraints associated with the choice of couplers
are the need for high directivity and the limitations on size due
to the requirement to integrate the instrument into a small
package.
[0051] As mentioned above, the preferred locations of the human
anatomy for the measurements to be carried out are the earlobe and
the web of the hand between the thumb and the first finger, since
these regions are rich in blood flow and are biologically simple in
structure. Ideally, the layers of tissue sandwiched between the
antennas 70,71, except the blood itself, will exhibit a constant
value of conductance and relative permittivity. An illustration of
a typical biological structure used with the instrument is shown in
FIG. 2, where it is assumed that the structure is symmetrical and
consists of only three tissue types; namely: skin 83, fat 84 and
blood 85. Of course, the structure will also contain water. The
thickness of the overall structure varies from between about 2 mm
and 20 mm, thus the propagation loss will be low. For example,
using a first order approximation, signal attenuation at a
frequency of 10 GHz will be as follows: blood=-1.5 dB/mm, dry
skin=-1.13 dB/mm and fat=-0.22 dB/mm.
[0052] In certain instances it may be preferable to perform
measurements in two directions using a single microwave source 10.
FIG. 3 shows an embodiment of the present invention to enable full
two port measurements to be made. The measurements could be a
combination, or all of, the following: transmission from first
antenna 70 through biological tissue 80 to second antenna 71,
reflection from biological tissue 80 back to first antenna 70,
transmission from second antenna 71 through biological tissue 80 to
first antenna 70, and reflection from biological tissue 80 back to
second antenna 71. An arrangement of electronically controllable
switches 30 is used to enable measurement direction change over to
take place automatically.
[0053] In the configuration shown in FIG. 3, three
single-pole-two-throw (SPDT) switches are used to enable the
microwave line-up 10, 170, 20 to be used as a microwave energy
source for both first antenna 70 and second antenna 71. In a first
configuration, as shown in FIG. 3, a first electronic switch SPDT1
31 provides the microwave energy from the amplifier 20 to a second
electronic switch SPDT2 32, which in turn provides the microwave
energy to the input of a transmission line 40, whose output is
connected to the input of a first matching filter 50. The output
from said first matching filter 50 is fed into the input of a first
directional coupler 60, which is configured as a forward power
coupler in an analogous manner to the arrangement shown in FIG. 1,
and whose coupled port is fed directly into the detector/receiver
unit 100. The output from the first coupler 60 is fed into the
input to second directional coupler 61, which in the illustrated
configuration is configured as a reverse power coupler and is used
to measure reflected forward power from the biological tissue
structure 80. A signal booster amplifier 21 is shown connected to
the coupled port of second coupler 61. This amplifier 21 is used to
increase the signal strength in the instance where the loss through
tissue structure 80 is high or the strength of the signal produced
by the microwave line-up 10,170,20 is inadequate. The output from
amplifier 21 is fed into the detector/receiver unit 100.
[0054] In the illustrated configuration, a third electronic switch
SPDT 3 33 is connected between ground through a 50.OMEGA. resistor
35 and the input of a further transmission line 41, whose output is
connected to the input of a second matching filter 51 (N.B. in this
switch configuration 51 is connected, but is not used). The output
from first matching filter 51 is fed into the input of a third
directional coupler 62, which is configured as a forward power
coupler and whose coupled port is fed directly into
detector/receiver unit 100 (N.B. in this switch configuration third
directional coupler 62 is not used). The output from the third
coupler 62 is fed into the input of a fourth directional coupler
63, which is configured as a reverse power coupler and in the
illustrated configuration is used to measure transmitted power from
the second antenna 71 after being transmitted through biological
tissue structure 80. A second signal booster amplifier 22 is shown
connected to the coupled port of the fourth directional coupler 63
and is provided for the same reasons as the first booster amplifier
21. The output from the second amplifier 22 is fed into the
detector/receiver unit 100. In this configuration the microwave
energy is transmitted by the first antenna 71 and received by the
first antenna 72.
[0055] A second configuration for electronic switches SPDT1 31,
SPDT2 32 and SPDT3 33 enables the microwave energy to be
transmitted by the first antenna 70 and received by the second
antenna 71. In the second configuration the first switch 31 is
connected to the third switch 33 to provide the output of the
amplifier 20 to the second transmission line 41, the third switch
33 no longer being connected to ground. The second switch now
connects the first transmission line 40 to ground via a 50 ohm
resistor 34. In this second configuration third coupler 62 measures
the transmitted microwave energy, fourth coupler 63 measures the
energy reflected back from the first antenna 70 and second coupler
61 measures the received microwave energy. First coupler 60 is not
used in this configuration.
[0056] The position of the switch contacts is controlled using
control signals generated by signal processor/controller 110. The
electronic switches 31, 32, 33 are preferably
micro-electro-mechanical systems (MEMS) based devices, PIN diode
based devices (reflective or absorptive) or metal oxide
semiconductor (MOS) devices, although other types of electronic
switch known to the skilled person may be used. The most suitable
device will be somewhat dependent upon the final frequency
used.
[0057] FIG. 4 shows an embodiment of the present invention for
measuring magnitude information only and detects positive or
negative peak values (maxima or minima) that occur in the magnitude
response over a frequency range of interest. As in FIG. 1, a
microwave source 10, signal attenuator 170 and low power amplifier
20 are provided, although in this embodiment the microwave source
10 is either a frequency synthesiser or a VCO, whose output
frequency can be swept over the range of interest by applying a
control voltage at the input. The frequency is monitored using
directional coupler 104, arranged such that the coupled port
measures a portion of forward directed power, and said coupled
portion of forward power is fed into a divider or frequency
pre-scalar 104 to provide a frequency that can be processed by a
signal processor/controller 110. The microwave energy signal is
transmitted through the biological tissue structure 80 using first
antenna 70 and, after propagation through said tissue structure 80,
the signal is received at second antenna 71. A magnitude detector
117 is used to detect the signal and a peak detector 118 is used to
detected the positive, or negative, going peak. The combination of
magnitude detector 117 and the peak detector 118 forms the
detector/receiver unit 100. The detected signal from the
detector/receiver unit 100 is then fed into the signal
processor/controller 110 where it is correlated with said frequency
information provided by the frequency divider 104. The magnitude
detector may take the form of a diode detector with appropriate
filtering, or a homodyne detector, which may use a mixer and a
local oscillator. Other types of magnitude detectors will be known
to a person skilled in the art. The processor/controller 110 is
used to determine the blood-glucose concentration from said
amplitude peak and corresponding frequency information. Said
processor/controller 110 also sends information to output device
120 whose function is to display the blood-glucose level in a
user-friendly format.
[0058] FIG. 5 shows a specific embodiment of the present invention
to enable both phase and magnitude information to be measured. In
this embodiment frequency mixers are used and operated such that
the local oscillator input frequency is different from that of the
RF input frequency. This provides two frequencies at the output of
said mixer; the sum of the local oscillator frequency and the RF
frequency and the difference between the RF frequency and the local
oscillator frequency. In this embodiment said local oscillator
frequency is derived from the microwave source 10. A portion of the
signal from said microwave source 10 is made available using a
first directional coupler 101 which is configured with its coupled
port arranged to measure a portion of the forward signal produced
by the microwave source 10. The coupled power from the first
directional coupler 101 is fed into frequency divider (pre-scalar)
104, where the frequency generated by the microwave source 10 is
divided by a fixed value (normally an integer) and is then
multiplied by a fixed value (normally an integer) to provide a
higher frequency using a frequency multiplier 105. The scaled
frequency output signal from the frequency multiplier 105 is fed
into a second directional coupler 102 and the output of the second
directional coupler 102 is fed into the first input, the local
oscillator input, of a first mixer 106. The second input to the
first mixer 106, the RF input, is taken from the coupled port of a
third directional coupler 60, which is configured to measure a
portion of the forward directed power being transmitted. The output
from first frequency mixer 106 is fed into a first integrated
phase/magnitude detector 109, which may be any commercially
available packaged phase/magnitude demodulator. The phase/magnitude
information produced by the phase/magnitude detector 109 is fed
into the signal processor/controller 110.
[0059] The scaled reference frequency taken from the output of the
frequency multiplier 105 is also used as the local oscillator
frequency inputs for a second and third frequency mixers 107, 108.
The first input, the local oscillator input, to the second mixer
107 is taken from the output of a fourth coupler 103, which in turn
receives the coupled output of the second coupler 102. The second
input, the RF input, going into said second mixer 107 is taken from
the coupled port of a fifth directional coupler 61, which is
configured to measure a portion of reflected power coming back via
first antenna 70 reflected back in the form of backscatter. The
output from the second frequency mixer 107 is fed into a second
integrated phase/magnitude detector 112. The phase/magnitude
information produced by 112 is fed into the signal
processor/controller 110. The first input, the local oscillator
input, to third mixer 108 is taken from the coupled port of fourth
directional coupler 103, whilst the second input, the RF input, to
the third mixer 108 is taken from the output of the second antenna
71 via a second matching filter 51, which matches the impedance of
the surface of the biological tissue structure 80 with the aperture
of second antenna 71. The output from said third frequency mixer
108 is fed into a third integrated phase/magnitude detector 111 and
the phase/magnitude information produced is fed into the signal
processor/controller 110.
[0060] Directional couplers 1, 2 and 4 (101, 102, 103) are
preferably 3 dB couplers or 3 dB splitters, and may take the form
of microstrip or stripline devices. It may be preferable to connect
low pass filters at the outputs of frequency mixers 106, 107, 108
to ensure that only the difference frequency (RF-Local oscillator
frequency) passes into phase/magnitude detectors 109, 112 and 111
respectively and that the sum frequencies produced by said
frequency mixers 106, 107 and 108 are rejected. In this embodiment
two low power amplifiers 20,21 are used to amplify the microwave
signal produced by microwave signal source 10, and first matching
filter 50 is used to provide a static impedance match between first
antenna 70 and the surface of the biological tissue structure
80.
[0061] An embodiment similar to that shown in FIG. 5 is given in
FIG. 6. This embodiment is similar to the embodiment shown in FIG.
5 and described above except that in this instance the three
frequency mixers 106, 107, 108 and the three phase/magnitude
detectors 109, 111, 112 are replaced by an electronically
controlled single-pole-three-throw switch (SP3T) 113, a single
mixer 106, and a single integrated phase/magnitude detector 109.
The advantage of this arrangement is that the noise produced by, or
injected into, frequency mixer 106 and phase/magnitude detector 109
is common to all phase/magnitude measurements taken from coupled
ports of third and fifth couplers 60, 61 and second matching filter
51, thus said noise signals can be subtracted from measurement
signals. The output from the coupled port of third directional
coupler 60 is connected to the first switch position of the
electronic switch 113. The third coupler may be used to measure the
level of forward energy that is being transferred into biological
tissue structure 80, or may be used as a reference to enable a
comparison to be made between the value of phase and magnitude
information measured at this position and that measured at other
locations. The output from the coupled port of fifth directional
coupler 61 is connected to the second switch position of the
electronic switch 113 and the output from second matching filter 51
is connected to the third switch position of the electronic switch
113. A control signal C6 is used to change the contact position
between the switch positions of the electronic switch 113. The
signal processor/controller 110 is used to determine the contact
position. The common output from the electronic switch 113 is
connected to the second input, the RF input, of the single
frequency mixer 106. The second input, the intermediate frequency,
to frequency mixer 106 is derived from frequency source 10 in a
similar manner to that discussed for the embodiment shown in FIG.
5, although the output from frequency multiplier 105 is fed
directly into the first input, the local oscillator input, of the
frequency mixer 106. Said frequency mixer 106 produces two
frequencies; the sum and the difference, but only the difference is
if interest in this embodiment of the current invention. It may be
preferable to insert a low pass filter at the output of said mixer
106 to filter out the sum frequency signal, but it is generally the
case that devices connected to the output of said frequency mixer
106 will not see the sum frequency due to the fact that the local
oscillator and the RF frequency are high microwave frequencies,
where high microwave frequency is defined here as being above 10
GHz in this instance. The output from said mixer 106, the
intermediate frequency output signal, is connected to an integrated
phase/magnitude detector 109 and the phase and magnitude
information output signals are connected to the signal
processor/controller 110. Preferably the insertion loss of the
channel between the input and output should be as low as possible
and the level of isolation between the switch contacts should be as
high as possible at the frequency of interest.
[0062] In preferred embodiments the microwave components are
integrated into a device compact that is enough to be carried on a
user's person, with the antennas either integrated into the same
device or coupled to the device by wired or wireless means. The
detector/receiver unit, signal processor and output device, or any
combination thereof, may also be integrated into the same package
as the microwave components or may be packaged separately with
appropriate signal communication means provided to the microwave
components. Transmission of the microwave energy, where required,
may be by co-axial via, co-axial cable, flexible waveguide or other
suitable medium known to the skilled person. Transmission of the
control and/or measurement signals may be by either known wired or
wireless techniques.
[0063] In wireless embodiments of the present invention the
integrated microwave assembly may take the form of a stand-alone
device, but more preferably are integrated into a commercially
available device in order to provide the facility for non-obtrusive
blood-glucose monitoring. Such devices may include Bluetooth.TM.
mobile telephone headsets, headphones, hearing aids or a standard
earphone. The detector/receiver unit, signal processor/controller
and output device are preferably integrated into a suitable
wireless device, such as a personal computer (PDA) that may be a
stand alone device or integrated within a mobile telephone, a
laptop computer or a wrist watch that contains a microprocessor.
The use of said personal computer will enable information
concerning, for example, blood-glucose level, to be displayed in
the form of a numerical value, for example, in mmol/L or mg/dL, or
provide a graph of blood-glucose level against time. Preferably the
wireless device is arranged to generate an audible warning to
advise the user that their blood-glucose level is outside a range
deemed to be acceptable and that corrective action is required.
Alternatively, the measurement information may be sent to a remote
monitoring station that is arranged to process said information and
display said information for a doctor, or other qualified person,
to monitor the patient's blood-glucose level. Said information may
be logged. The sent data may have been processed by the wireless
device or may be unprocessed, in which case the signal
processor/controller may be provided at the remote location.
[0064] Antenna structures 70, 71 suitable for use in the current
invention will now be considered. There are a number of features
that are preferred for said antenna structures to be appropriate
for use in embodiments of the current invention and these are
listed below:
[0065] It is preferable for said antenna structure(s) 70, 71 to be
flexible and manufactured to be conformal with the biological
tissue structure 80;
[0066] It is preferable for the surface of said antenna(s) 70, 71
to be in direct contact with the surface of said biological
structure 80 and for said surface of antenna(s) 70, 71 to be coated
with a biocompatible material;
[0067] It is preferable for the antenna feed line(s) 128, 129 to be
located on a surface within the antenna structure that is not the
same as the antenna aperture or the radiating surface;
[0068] It is preferable for the feed line(s) 128, 129 to be
impedance matched to the input impedance of said antenna(s) 70,71
to prevent reflections occurring at said feed point;
[0069] It may be preferable for said antenna(s) 70,71 to radiate
microwave energy at a single spot frequency that capture the
resonant responses and a shift thereof caused by changes in
concentration of constituents;
[0070] It may be preferable for said antenna(s) 70, 71 to be
capable of radiating microwave energy over a band of microwave
frequencies;
[0071] It may be preferable for said antenna(s) 70, 71 to be
capable of radiating microwave energy at a plurality of spot
frequencies;
[0072] It may be preferable for the radiating elements of said
antenna(s) 70, 71 to be impedance matched to the surface of the
biological tissue;
[0073] It may be preferable for the radiating elements of said
antenna(s) 70, 71 to be impedance matched with biological tissue
contained within the tissue structure used for the
measurements;
[0074] It may be preferable for said antenna(s) 70, 71 to radiate
microwave energy at a plurality of microwave frequencies and each
of the said microwave frequencies to have a finite bandwidth and
the said frequencies to be spaced far enough apart to ensure that
band overlapping cannot occur;
[0075] It is preferable for the surface area of said antenna(s) 70,
71 to be small enough to enable a pair of said antennas, or a
single antenna and a reflective plate, to be attached to the human
anatomy in a region where the volume of biological tissue structure
80 available for attachment to be made is limited, for example, the
earlobe or the web of the hand between the first finger and the
thumb;
[0076] It is preferable for the structure of said antenna(s) 70, 71
to be non-obtrusive;
[0077] It may be preferable for the radiation pattern produced by
said antenna(s) 70, 71 to have a high directivity;
[0078] It is preferable for said antenna(s) 70, 71 to provide a
gain with respect to an isotropic radiator of greater than 0
dBi;
[0079] Antenna structures found to be appropriate for use in this
invention include: patch antennas, spiral antennas, loaded/unloaded
waveguide antennas and radiating slot antennas. Other antenna
structures may also be suitable for use in certain applications of
the current invention and these will be known to a person
experienced in the art of antenna/microwave engineering.
[0080] FIG. 7 shows biological tissue structure 80 sandwiched
between a pair of patch antenna 70,71 with clip 90 and fastener 91
used to ensure alignment between said antenna pair 70,71 and to
attach said antenna pair 70,71 to the human anatomy. The first
antenna assembly 70 and the second antenna assembly 71 are
identical, and comprise: a radiating patch 74, 77, a coaxial feed
128, 129, a dielectric material or substrate 75, 78, a ground plane
76, 79, and a co-axial connector 137, 138. Said co-axial connector
may take a number of forms, for example, sub-miniature A (SMA), SMB
or SMC or another miniature microwave connector that is capable of
working at the frequency (ies) of operation relevant to this
invention. The arrangement shown in FIG. 7 enables both
transmission and reflection (backscatter) measurements to be
performed. In further embodiments the second antenna 71 may be
replaced by a reflecting plate, in which case reflection
(backscatter) only can be measured. The construction of a
rectangular patch antenna consisting of a single patch is shown in
FIG. 8, where the microwave energy is launched into the radiating
patch 74, 77 using a microstrip feed line 128, 129 that is
fabricated on the same surface 75, 78 as said radiating patch 74,
77. Said surface 75, 78 is a substrate material that may consist of
a relative permittivity (dielectric loading constant) and/or a
relative permeability (magnetic loading constant) of greater than
unity, which is used to shrink the size of said radiating patch 74,
77. A ground plane 76, 79 is attached to the underside of substrate
material 75, 78. It is preferable for the area of said ground plane
75/78 to be greater than the area of said radiating patch 74, 77.
Dimensions that are of importance to ensure efficient energy
propagation from said radiation patch 75, 77 are: patch width (W),
patch length (L) and substrate thickness (t); these dimensions are
indicated in FIG. 8. It is preferable for W to be comparable to the
wavelength at the desired frequency of operation in order to
enhance the radiation emitted from the edges of said radiating
patch 74, 77. For the fundamental TM.sub.10 mode to propagate, the
length L should be slightly less than .lamda./2, where .lamda. is
the wavelength in substrate material 75, 78.
[0081] If the patches are considered as cavity resonators (boxes)
with four out of the eight sides missing then the radiation from
said patch antennas 70, 71 is the result of energy leaking out of
the resonant cavities (radiation is primarily due to energy leaking
from the two gaps of width W). As stated previously, the thickness
t of the substrates 75, 78 is typically small relative to the other
dimensions of said patches 74, 77 therefore the energy leaking out
of the boxes is much smaller than the energy stored within it. In
order to achieve wide bandwidth operation, it is necessary to use
the substrate material 75, 78 with the highest thickness t and
lowest relative permittivity .epsilon..sub.r (this assumes only
dielectric loading) that is practically possible. These
requirements of course may conflict with the requirement to make
the patch size as small as possible and also provide a matched feed
line. Possible candidates for substrate material 75, 78 are as
follows: semi-insulating GaAs (.epsilon..sub.r=13), silicon
(.epsilon..sub.r=11.9, PTFE-ceramic, composite
(.epsilon..sub.r=10.2), silicon resin-ceramic (.epsilon..sub.r=3 to
25) and Ferrite (.epsilon..sub.r=9 to 16). Materials for the
radiating patches 74, 77, the ground-planes 76, 79 and the feed
lines 128, 129 may include, but is not limited to: copper, brass,
silver, silver platted copper and aluminium. It may be desirable to
cover said radiating patch with an insulating material and it may
be preferable for said insulating material to be biocompatible.
Said insulating cover will affect the performance of said antennas
70, 71 and so the effect of including said cover must be
considered. A dielectric cover will cause the resonant frequency of
the patch antenna 70, 71 (f.sub.o) to be lowered, therefore the
antenna structure without the cover must be designed to resonate at
a slightly higher frequency than the desired operating frequency,
or the frequency at the centre of the band of operating
frequencies. In general, when said patches 74, 77 are covered with
a dielectric, the following properties will change: .epsilon..sub.r
eff, losses, Q-factor and directive gain. The change in
.epsilon..sub.r eff causes the greatest change and the amount of
change is dependent upon the thickness t and the relative
permittivity .epsilon..sub.r of the substrate. The presence of said
cover also produces a change in the near/far field radiation
patterns.
[0082] In designing the most appropriate antenna construction, it
is preferable for the feed lines 128, 129 not to be on the same
surface as the radiating patches 74, 77 due to the fact that said
feed lines 128, 129 will also radiate energy into the biological
tissue structure 80 and reduce the effectiveness of the antennas
radiating into the tissue. This factor becomes most important when
the instrument is operated at high microwave frequencies and high
values of relative permittivity and/or relative permeability are
used as the substrate material 75, 78, due to these factors causing
the radiating patches 74, 77 to become very small. FIG. 26
illustrates an alternative form of antenna feed, the co-axial feed.
In this arrangement, the centre conductor of the coaxial connector
forms feed lines 128, 129 and said feed lines 128,129 are soldered
to the radiating patches 74, 77. The main advantage of this feed
system is that the position of the feed-point determines the input
impedance of the patch 74, 77 and so the feed-point can be simply
moved around t0 adjust said input impedance. The disadvantages are
that a hole has to be drilled in the substrate 75, 78 and the
connector protrudes outside the bottom of the ground plane 76, 79,
thus the structure is not completely coplanar. Also, to achieve
wide bandwidth operation, a thick substrate 75, 78 is required and
so the probe (or pin) length becomes longer, which can give rise to
increased spurious radiation emission from the probe, increased
surface wave power, and increased feed inductance. However, the
feed inductance can be compensated for using, for example, a series
connected capacitor. One approach used to introduce said series
capacitor is to etch out an annular slot in the patch metallization
concentric with the probe. All other parameters are the same as
those discussed with reference to FIG. 8. FIG. 27 shows an
alternative feed arrangement whereby the feed line 128, 129 is
electromagnetically (or capacitively) coupled to the radiating
patch 74, 77. In this arrangement the substrate layer 75, 78 is
made up of two separate dielectric (and/or magnetic) materials and
said materials may have different values of relative permittivity
(and/or relative permeability). Said feed line 128, 129 is
sandwiched between said substrate layers 75, 78, which are
themselves placed between said radiating patch 74, 77 and ground
plane 76, 79. This method of coupling microwave energy into the
radiating patches 74, 77 is also known as proximity coupling and
the advantage of this feed configuration is that spurious
feed-network radiation coupled into the biological tissue structure
80 is eliminated. Careful choice of the two different relative
permittivity values for the substrate material 75, 78 (one for the
patch 74, 77 and one for the feed line 128, 129) can be used to
optimise the overall performance of the antenna 70, 71. The
increased overall thickness of the substrate 75, 78, and the fact
that two dielectric materials are now in series, can be used to
increase the bandwidth of operation. It may be preferable to
include a balanced-to-unbalanced (balun) transformer with certain
arrangements to match the unbalanced co-axial, or microstrip, feed
128, 129 to the balanced antenna 70, 71.
[0083] If a horn antenna or loaded rectangular/cylindrical
waveguide antenna structure is used and the physical dimensions are
such that is possible to support the dominant TE.sub.10/TE.sub.11
modes of propagation in air, i.e. .epsilon..sub.r is unity, then it
is not required to load the antenna structure with a dielectric or
magnetic material. On the other hand, if a horn antenna, or a
loaded rectangular/cylindrical waveguide antenna structure is used
and the physical dimensions are such that is not possible to
support the dominant TE.sub.10/TE.sub.11 modes of propagation in
air then the antenna must be loaded with a suitable dielectric or
magnetic material whose relative permittivity/permeability is
greater than unity. The horn antenna structure must be designed to
couple well into the surface of the skin, or other biological
material that is of interest. This may be achieved by inserting
tuning stubs into the broad wall of the antenna feed line.
[0084] In further embodiments of the present invention the antennas
preferably consist of fine needle structures that can be partially,
or, in some instances, fully inserted into the biological tissue.
Possibly antenna structures for these embodiments include co-axial
and loaded waveguide antennas. For the latter construction, the
preferred shape is the cylinder. For the co-axial structure it is
preferable to insert only the centre conductor in to the biological
tissue. It is also preferable for the outside diameter of the
overall co-axial structure to be less than 0.5 mm, and more
preferably less than 0.15 mm. It is also preferable for the
diameter of the centre conductor of the co-axial structure to be
less than 0.2 mm, and more preferably less than 0.05 mm. A further
antenna structure that may be preferable for non-invasive
measurements is the slotted line antenna structure, where the face
of the antenna that is in contact with the skin is a complete
ground plane except for a slot that radiates energy into tissue. A
dielectric material is connected to the opposite side of the ground
plane and a microstrip line is arranged over the slot to enable
energy to be coupled into the slot and into tissue. The feed-line
is on the same side as the radiating microstrip, thus problems
associated with feed line coupling into tissue are overcome. The
slotted line antenna may be the antenna of choice.
[0085] A typical setup showing an antenna arrangement piercing
biological tissue structures to varying depths of penetration is
shown in FIG. 3, which shows a first antenna arrangement 60, 74, 75
mounted to the surface of the skin with the needle antenna 74
penetrating through the skin (epidermis and dermis) 83, the fat
layer 84, and into blood 85, and a second antenna arrangement 61,
78, 79 is shown connected to the opposite side of the tissue
structure where needle antenna 78 also penetrates as far as the
region containing blood 85. A similar arrangement may be provided
in which the first and second antennas are mounted adjacent to one
another on the same side of tissue structure 80. Alternatively,
only a single needle antenna may be provided mounted on the surface
of the skin 83. In this arrangement the single antenna is used to
both transmit microwave energy and measure reflected energy. In all
three previous arrangements the needle 74 may be arranged to
penetrate into the skin only to the depth of the lower epidermis or
the dermis. In the arrangement shown in FIG. 9 the female coaxial
connector 75/79 is connected to a biocompatible patch 60/61 and
dielectric material is provided between the inner and outer
conductors 37/77. The dielectric material 73/77 is flush with the
bottom of the biocompatible patch (or pad) 60,61 and the inner
conductor needle (or pin) is shown protruding through the bottom of
said patch 60/61.
[0086] In the arrangement shown in FIG. 9 only the centre conductor
78, 74 is arranged to be inserted into the tissue structure(s).
However, in other embodiments the antenna may be arranged such that
the complete co-axial antenna can be inserted into the tissue. In
these co-axial antenna structures it is preferable for the outside
diameter of the overall co-axial structure 72/76 to be less than
0.5 mm, and more preferably less than 0.15 mm. It is also
preferable for the diameter of the centre conductor 74/78 to be
less than 0.2 mm, and more preferably less than 0.05 mm. The length
of the portion of the centre conductor to be inserted into the
tissue will be dependent upon the dielectric constant of the
tissue. In general, the length in free space will be shortened by
the inverse of the square root of the relative permittivity of the
biological tissue 80. It is preferable to coat the inner conductor
74/78 with a conformal coating of biologically acceptable material.
In the instance where the complete co-axial antenna structure is
inserted into the biological tissue, a portion of, or, in some
cases the complete, co-axial structure may be coated with a
biologically compatible material.
[0087] FIG. 10 shows a dielectric loaded waveguide antenna
structure according to further embodiments of the present
invention. A cylindrical waveguide is loaded with a material that
exhibits a low loss at the frequency of interest, and has a high
relative permittivity in order to shrink the diameter of the
structure to a value that is acceptable in terms of piercing the
skin whilst causing a minimal degree of discomfort. The arrangement
shown in FIG. 10 shows the microwave signal launched into the
waveguide probe using an E-field probe 71 connected to a co-axial
microwave connector 75/79. In the arrangement shown, a waveguide
cavity 70 is used to launch the dominant TE.sub.11 mode into the
waveguide. Ideally, the distance between the E-field probe and the
closed back wall of 70 is a quarter wavelength (or an odd multiple
thereof) at the frequency of operation.
[0088] In some embodiments of the present invention the centre
conductor of the antenna shown in FIGS. 9 & 10 may be hollow
and in fluid communication with a source of medicament. For
example, where the constituent concentration being measured is the
blood-glucose level of an individual, the antenna may be connected
to a source of insulin. This allows the apparatus of embodiments of
the present invention to be used as part of a closed loop system,
wherein the medicament, or other desired fluid, can be administered
to an individual automatically according to the measured
constituent concentration.
[0089] FIGS. 37 and 38 respectively show the magnitude and phase
responses obtained using apparatus according to embodiments of the
present invention to investigate two blood-glucose solutions having
glucose concentrations of 6 mmol/L and 14 mmol/L respectively. The
magnitude and phase responses were measured over a frequency range
of 11.5 GHz to 15.5 GHz. FIG. 11 shows the recorded magnitude
response, with magnitude shown on the Y axis and given in decibels
with reference to a milli-Waft (dBm), and frequency shown on the X
axis and given in gigahertz (GHz), with the amplitude being
expressed as the ratio between the received, or reflected,
microwave energy and the transmitted energy, i.e. the output
energy/input energy. The curve representing the 6 mmol/L glucose
concentration is shown using a solid line and the curve
representing the 14 mmol/L concentration is shown using a dotted
line. It can be seen that a minimum occurs for each concentration
and that there is a marked difference in frequency between the
positions of said minimums. For the 6 mmol/L glucose concentration
the minimum occurs at 13.130 GHz and for the 14 mmol/L glucose
concentration the minimum occurs at 13.452 GHz, thus a frequency
shift of 322 MHz has been observed here.
[0090] Multiple reflections of the microwave field will take place
between the faces of the two antennas such that both the net
transmitted power and the net reflected power are a result of the
phase lag that exists between each reflected wave. This phase lag
is a function of both the distance between the antennas, equal to
the thickness of the tissue structure, and the real part of the
dielectric constant of the tissue structure & biological
solution therein (typically blood).
[0091] The path difference d, between successive waves is given
by:
d=2. .epsilon..sub.r.t
where .epsilon. is the dielectric constant of the material of
interest, and t is the physical length of the path in the material.
Each reflected wave will lag in phase by an amount given by:
.delta.=2.pi.2. .epsilon..sub.r.t/.lamda.
where .lamda. is the free space wavelength of the microwave
radiation. Both the transmitted power and the reflected power are a
result of the superposition of the multiple reflections. The
reflected intensity can be represented by Airy's formula and is
given by:
Ir={4.R.sin.sup.2(.delta./2)}/{(1-R).sup.2+4.R.sin.sup.2(.delta./2)}
[0092] Where R is the fraction of the intensity reflected on a
single reflection. For a lossless medium the transmitted intensity,
It, must be given by:
Ir=1-It
[0093] And so Airy's formula for the transmitted intensity would
be:
It=(1-R).sup.2/{(1-R).sup.2+4.R.sin.sup.2(.delta./2)}
[0094] However, the tissue structure is not lossless and the
material sample will have a fractional intensity absorption
coefficient A. Hence in the formula above (1-R) should be replaced
by (1-R-A).
[0095] When sin.sup.2(.delta./2)=0, this is a maximum and occurs
when:
2. ..epsilon..sub.rt=n..lamda. n being an integer.
[0096] However, minima occur at:
2. .epsilon..sub.r.t=(n+1/2)..lamda.
[0097] FIG. 11 shows the case where a minimum has occurred in the
transmitted power and hence the situation represented by this last
equation had been set up. The two measured frequencies for the
different blood samples can be converted to free space wavelength
(.lamda.). Knowing the physical path length of the sample
.epsilon..sub.r can be calculated.
[0098] A further property of the biological tissue structures that
can be utilised in embodiments of the present invention is that the
quality factor Q of the tissue varies with the concentration of the
constituent to be measured. The quality factor, or Q factor, is a
measure of the rate at which a vibrating system dissipates its
energy, or alternatively expressed as the ratio of the energy
stored in the vibrating system to the energy dissipated. A higher Q
factor indicates a lower rate of dissipation. When the system is
driven, its resonant behavior depends strongly on Q. Resonant
systems respond to frequencies close to their natural frequency
much more strongly than they respond to other frequencies. A system
with a high Q resonates with a greater amplitude (at the resonant
frequency) than one with a low Q factor, and its response falls off
more rapidly as the frequency moves away from resonance. This can
be seen with reference to FIG. 11, where the amplitude response for
the 6 mmol/L solution decays more rapidly away from the minimum
than for the 14 mmol/L solution, indicating that the Q factor for
the 6 mmol/L solution is higher than that of the 14 mmol/L
solution. The Q factor of a system can also be determined from the
ratio of the resonant frequency to the -3 dB bandwidth (the
frequency bandwidth between the frequencies on either side of the
resonant frequency at which the amplitude has decayed by 3 dB [half
the peak power] from the resonant peak amplitude). Consequently, in
embodiments of the present invention the Q factor for a tissue
structure under investigation can be directly derived from the
amplitude response and the Q factor correlated to the concentration
of the constituent in the tissue structure.
[0099] FIG. 12 shows the phase response of the ratio of the
received, or reflected, energy to the transmitted energy, where
phase is shown on the Y axis and is given in degrees and frequency
is shown on the X axis and is given in GHz. The curve representing
the 6 mmol/L glucose concentration is shown using a solid line and
the curve representing the 14 mmol/L concentration is shown using a
dotted line. It can be seen that there is a phase change between
the 6 mmol/L glucose concentration and the 14 mmol/L glucose
concentration and that the maximum change occurs at a frequency of
approximately 13.130 GHz. At this frequency the phase for the 6
mmol/L glucose concentration is 122.degree. and the phase for the
14 mmol/L concentration is 82.degree., giving a phase difference of
40.degree.. It can be concluded from these result that there is a
marked change in the frequency at which a minimum occurs in the
magnitude response for two representative blood-glucose
concentrations and there is also a marked change in the phase when
two blood-glucose solutions of the same volume were measured.
[0100] Since there will be a variation in the thickness of the
biological tissue structure between individuals, the resonant
frequency, and possibly the Q or shape of the transmission curve,
of the tissue structure for any given constituent concentration
will vary from individual to individual. Therefore, before a valid
measurement for an individual can be made it is necessary to know
the thickness of the tissue structure. Once the thickness is known,
calibration curves can be used to establish the resonant frequency
for the structure for various constituent concentrations. A number
of methods can be used to automatically measure the thickness:
[0101] a) A digital micrometer method; [0102] b) A measure of
change in resistance using a contact to a resistive material;
[0103] c) A low frequency capacitance measurement; [0104] d)
Optical displacement sensor.
[0105] In embodiments of the present invention it is convenient to
take a low frequency capacitance measurement. To do this it is
necessary to assume that the bulk change in relative permittivity
of the tissue structure between individuals is negligible at the
frequency of interest (for example, 1 KHz or 10 KHz), and that the
capacitance is thus directly proportional to the frequency.
Consequently, the micro-strip antenna structures of embodiments of
the present invention can be used to form the plates of the
parallel plate capacitor and a fixed value stable inductor is
additionally used to form the low frequency resonant circuit. The
capacitor formed by the antenna plates and the biological structure
are resonated with the fixed inductor to produce a resonant
frequency from which the thickness could be calculated.
* * * * *